Unraveling the molecular basis for ligand binding in truncated hemoglobins: The trHbO Bacillus subtilis case
Truncated hemoglobins (trHbs) are heme proteins present in bacteria, unicellular eukaryotes, and higher plants. Their tertiary structure consists in a 2-over-2 helical sandwich, which display typically an inner tunnel/cavity system for ligand migration and/or storage. The microorganism Bacillus subt...
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paper:paper_08873585_v78_n4_p962_Boechi2023-06-08T15:46:47Z Unraveling the molecular basis for ligand binding in truncated hemoglobins: The trHbO Bacillus subtilis case Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel B. Subtilis Ligand migration Molecular dynamics Truncated hemoglobin carbon monoxide oxygen truncated hemoglobin bacterial protein article Bacillus subtilis controlled study deoxygenation ligand binding molecular dynamics oxygenation priority journal protein structure simulation Bacillus subtilis chemistry enzyme active site kinetics metabolism protein secondary structure Bacillus subtilis Embryophyta Protista Bacillus subtilis Bacterial Proteins Carbon Monoxide Catalytic Domain Kinetics Molecular Dynamics Simulation Oxygen Protein Structure, Secondary Truncated Hemoglobins Truncated hemoglobins (trHbs) are heme proteins present in bacteria, unicellular eukaryotes, and higher plants. Their tertiary structure consists in a 2-over-2 helical sandwich, which display typically an inner tunnel/cavity system for ligand migration and/or storage. The microorganism Bacillus subtilis contains a peculiar trHb, which does not show an evident tunnel/cavity system connecting the protein active site with the solvent, and exhibits anyway a very high oxygen association rate. Moreover, resonant Raman results of CO bound protein, showed that a complex hydrogen bond network exists in the distal cavity, making it difficult to assign unambiguously the residues involved in the stabilization of the bound ligand. To understand these experimental results with atomistic detail, we performed classical molecular dynamics simulations of the oxy, carboxy, and deoxy proteins. The free energy profiles for ligand migration suggest that there is a key residue, GlnE11, that presents an alternate conformation, in which a wide ligand migration tunnel is formed, consistently with the kinetic data. This tunnel is topologically related to the one found in group I trHbs. On the other hand, the results for the CO and O 2 bound protein show that GlnE11 is directly involved in the stabilization of the cordinated ligand, playing a similar role as TyrB10 and TrpG8 in other trHbs. Our results not only reconcile the structural data with the kinetic information, but also provide additional insight into the general behaviour of trHbs. © 2009 Wiley-Liss, Inc. Fil:Boechi, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08873585_v78_n4_p962_Boechi http://hdl.handle.net/20.500.12110/paper_08873585_v78_n4_p962_Boechi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
B. Subtilis Ligand migration Molecular dynamics Truncated hemoglobin carbon monoxide oxygen truncated hemoglobin bacterial protein article Bacillus subtilis controlled study deoxygenation ligand binding molecular dynamics oxygenation priority journal protein structure simulation Bacillus subtilis chemistry enzyme active site kinetics metabolism protein secondary structure Bacillus subtilis Embryophyta Protista Bacillus subtilis Bacterial Proteins Carbon Monoxide Catalytic Domain Kinetics Molecular Dynamics Simulation Oxygen Protein Structure, Secondary Truncated Hemoglobins |
| spellingShingle |
B. Subtilis Ligand migration Molecular dynamics Truncated hemoglobin carbon monoxide oxygen truncated hemoglobin bacterial protein article Bacillus subtilis controlled study deoxygenation ligand binding molecular dynamics oxygenation priority journal protein structure simulation Bacillus subtilis chemistry enzyme active site kinetics metabolism protein secondary structure Bacillus subtilis Embryophyta Protista Bacillus subtilis Bacterial Proteins Carbon Monoxide Catalytic Domain Kinetics Molecular Dynamics Simulation Oxygen Protein Structure, Secondary Truncated Hemoglobins Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel Unraveling the molecular basis for ligand binding in truncated hemoglobins: The trHbO Bacillus subtilis case |
| topic_facet |
B. Subtilis Ligand migration Molecular dynamics Truncated hemoglobin carbon monoxide oxygen truncated hemoglobin bacterial protein article Bacillus subtilis controlled study deoxygenation ligand binding molecular dynamics oxygenation priority journal protein structure simulation Bacillus subtilis chemistry enzyme active site kinetics metabolism protein secondary structure Bacillus subtilis Embryophyta Protista Bacillus subtilis Bacterial Proteins Carbon Monoxide Catalytic Domain Kinetics Molecular Dynamics Simulation Oxygen Protein Structure, Secondary Truncated Hemoglobins |
| description |
Truncated hemoglobins (trHbs) are heme proteins present in bacteria, unicellular eukaryotes, and higher plants. Their tertiary structure consists in a 2-over-2 helical sandwich, which display typically an inner tunnel/cavity system for ligand migration and/or storage. The microorganism Bacillus subtilis contains a peculiar trHb, which does not show an evident tunnel/cavity system connecting the protein active site with the solvent, and exhibits anyway a very high oxygen association rate. Moreover, resonant Raman results of CO bound protein, showed that a complex hydrogen bond network exists in the distal cavity, making it difficult to assign unambiguously the residues involved in the stabilization of the bound ligand. To understand these experimental results with atomistic detail, we performed classical molecular dynamics simulations of the oxy, carboxy, and deoxy proteins. The free energy profiles for ligand migration suggest that there is a key residue, GlnE11, that presents an alternate conformation, in which a wide ligand migration tunnel is formed, consistently with the kinetic data. This tunnel is topologically related to the one found in group I trHbs. On the other hand, the results for the CO and O 2 bound protein show that GlnE11 is directly involved in the stabilization of the cordinated ligand, playing a similar role as TyrB10 and TrpG8 in other trHbs. Our results not only reconcile the structural data with the kinetic information, but also provide additional insight into the general behaviour of trHbs. © 2009 Wiley-Liss, Inc. |
| author |
Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_facet |
Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_sort |
Boechi, Leonardo |
| title |
Unraveling the molecular basis for ligand binding in truncated hemoglobins: The trHbO Bacillus subtilis case |
| title_short |
Unraveling the molecular basis for ligand binding in truncated hemoglobins: The trHbO Bacillus subtilis case |
| title_full |
Unraveling the molecular basis for ligand binding in truncated hemoglobins: The trHbO Bacillus subtilis case |
| title_fullStr |
Unraveling the molecular basis for ligand binding in truncated hemoglobins: The trHbO Bacillus subtilis case |
| title_full_unstemmed |
Unraveling the molecular basis for ligand binding in truncated hemoglobins: The trHbO Bacillus subtilis case |
| title_sort |
unraveling the molecular basis for ligand binding in truncated hemoglobins: the trhbo bacillus subtilis case |
| publishDate |
2010 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08873585_v78_n4_p962_Boechi http://hdl.handle.net/20.500.12110/paper_08873585_v78_n4_p962_Boechi |
| work_keys_str_mv |
AT boechileonardo unravelingthemolecularbasisforligandbindingintruncatedhemoglobinsthetrhbobacillussubtiliscase AT martimarceloadrian unravelingthemolecularbasisforligandbindingintruncatedhemoglobinsthetrhbobacillussubtiliscase AT estrindarioariel unravelingthemolecularbasisforligandbindingintruncatedhemoglobinsthetrhbobacillussubtiliscase |
| _version_ |
1768543616452526080 |